Journal of Supportive Oncology - Online 1st

Cancer (Journal Of The American Cancer Society)

New England Journal of Medicine

Tuesday, July 21, 2015

Akathisia

Akathisia (from the Greek καθίζειν: inability to sit) is one of the most prevalent and distressful psychotropic-induced extrapyrimidal adverse effects. It is a neuropsychiatric syndrome characterized by both subjective (inner feeling) and objective (physical symptoms) restlessness.

Due to this inner restlessness, patients may experience fidgeting, pacing, rocking while standing or sitting, crossing and uncrossing legs while sitting, and constant movement of the feet. Patients have also described these feelings as “wanting to jump out of my skin”and as a “crawling skin sensation.” (4)

Among the drugs used to treat delirium, haloperidol, might be the antipsychotic with the highest risk for development of akathisia. (5) The risk for akathisia in patients with delirium taking antipsychotics appears to be a dose-related phenomenon. Effective and well tolerated treatment is a major unmet need in akathisia that merits a search for new remedies.

Assessment Scales

"Studies using specific scales for evaluation of akathisia in delirium are lacking. Some populations, such as patients with cancer or terminally ill patients in palliative care settings taking antipsychotics for the treatment of delirium, could be at higher risk for development of akathisia as a side effect." (5)

Treatment

Early management of akathisia is important because it may be associated with poor treatment response and medication noncompliance, and most importantly is distressing to the patient and caregivers. Unfortunately many patients fail to respond to standard management of akathisia (typically benzodiazepines, beta blockers, anticholinergic agents). As medications used to alleviate akathisia symptoms such as anticholinergics and benzodiazepines could potentially worsen delirium, management of akathisia among delirious patients on antipsychotics should be further studied to explore the efficacy of other agents.

In addition to dopaminergic mechanisms, it has been hypothesized that serotonin may play a prominent role in the pathophysiology of akathisia.

Trazodone is an antidepressant agent demonstrating prominent serotonergic antagonistic properties. An open-label pilot study investigated the efficacy of trazodone in the management of akathisia. Nine female patients with a score of at least “mild akathisia” on the Barnes Akathisia Scale, and receiving a stable dose of antipsychotic medication, were administered trazodone, titrated up to a dosage of 100 mg/day over a period of 5 days. The patients demonstrated marked improvement in symptoms of akathisia. In addition, some improvement was noted in symptomatology of anxiety, depression, and psychosis. (3)

Low-dose mirtazapine was found to be efficacious for neuroleptic-induced akathisia. (2) "The
most compelling evidence indicating that 5-HT2A antagonists may represent a new
class of effective anti-akathisia agent comes from the largest-to-date
randomised controlled trial comparing low-dose mirtazapine with propranolol in
90 patients with FGA-induced (first-generation antipsychotics) acute akathisia. Mirtazapine is characterised by
potent presynaptic alpha-2 adrenergic antagonism, which accounts for its
antidepressant activity, and marked 5-HT2A blockade that seems to preponderate
in a low dose and contribute to its anti-akathisia properties. Mirtazapine,
given once daily (15 mg) was as effective as propranolol (80 mg twice daily) in
producing a greater improvement in akathisia compared with placebo (reduction
in BARS global scale: 1.10 (s.d. = 1.37) points (34%) and 0.80 (s.d. = 1.11)
points (29%) v. 0.37 (s.d. = 0.72) points (11%) respectively; P = 0.036).
Responder analysis (BARS global scale reduction 52) yielded a similar robust
anti-akathisia effect in mirtazapine and propranolol v. placebo (43.3% and 30%
v. 6.7% respectively; P = 0.005). Low numbers needed to treat (3 and 4
respectively) support high clinical efficacy of both compounds. Importantly,
mirtazapine achieved an anti-akathisia effect with more convenient dosing than
propranolol and better tolerability, with mild transient sedation as the only
observed side-effect. The favourable mirtazapine safety profile was also
supported by the absence of significant changes in vital signs." (1)

Suggested Approach

Discontinue [alternatively, dose decrease] the offending agent. If this is not possible or ease of symptoms is required, when the decision is to add an anti-akathisia agent

propranolol (40–80 mg/day twice daily) or

low-dose mirtazapine (15 mg once daily) as first-line treatment have the most supportive evidence.

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Pharmacy History

"The earliest known compilation of medicinal substances was ARIANA the Sushruta Samhita, an Indian Ayurvedic treatise attributed to Sushruta in the 6th century BC. However, the earliest text as preserved dates to the 3rd or 4th century AD.Many Sumerian (late 6th millennium BC - early 2nd millennium BC) cuneiform clay tablets record prescriptions for medicine.[3]

Ancient Egyptian pharmacological knowledge was recorded in various papyri such as the Ebers Papyrus of 1550 BC, and the Edwin Smith Papyrus of the 16th century BC.

The earliest known Chinese manual on materia medica is the Shennong Bencao Jing (The Divine Farmer's Herb-Root Classic), dating back to the 1st century AD. It was compiled during the Han dynasty and was attributed to the mythical Shennong. Earlier literature included lists of prescriptions for specific ailments, exemplified by a manuscript "Recipes for 52 Ailments", found in the Mawangdui tomb, sealed in 168 BC. Further details on Chinese pharmacy can be found in the Pharmacy in China article."

Journal of Palliative Medicine - Table of Contents

Traditional Romanian Pharmacy

The Sibiu Pharmacy Museum in Sibiu, Transylvania, Romania, is housed in a 1569 Gothic townhouse where the oldest pharmacy in Romania operated for over 150 years. The pharmacy was known as La Ursul Negru (The Black Bear).

Sir William Osler: "It is much more important to know what sort of a person has a disease than what sort of disease a patient has."

William Osler is regarded as McGill’s most eminent medical graduate and, as Professor of the Institutes of Medicine, the most eminent member of the McGill Medical Faculty. At the time of his death (1919), he was without question the best known and best loved physician in the English-speaking world.